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Bisphenol AF-induced endogenous transcription is mediated by ER? and ERK1/2 activation in human breast cancer cells.


ABSTRACT: Bisphenol AF (BPAF)-induced transcriptional activity has been evaluated by luciferase reporter assay. However, the molecular mechanism of BPAF-induced endogenous transcription in human breast cancer cells has not been fully elucidated. In the present study, we investigated the effect and mechanism of BPAF-induced endogenous transcription detected by real-time PCR in human breast cancer cells. We found that BPAF stimulated transcription of estrogen responsive genes, such as trefoil factor 1 (TFF1), growth regulation by estrogen in breast cancer 1 (GREB1) and cathepsin D (CTSD), through dose-dependent and time-dependent manners in T47D and MCF7 cells. Gene-silencing of ER?, ER? and G protein-coupled estrogen receptor 1 (GPER) by small interfering RNA revealed that BPAF-induced endogenous transcription was dependent on ER? and GPER, implying both genomic and nongenomic pathways might be involved in the endogenous transcription induced by BPAF. ER?-mediated gene transcription was further confirmed by inhibition of ER activity using ICI 182780 in ER?-positive T47D and MCF7 cells as well as overexpression of ER? in ER?-negative MDA-MB-231 breast cancer cells. Moreover, we utilized Src tyrosine kinase inhibitor PP2 and two MEK inhibitors PD98059 and U0126 to elucidate the rapid nongenomic activation of Src/MEK/ERK1/2 cascade on endogenous transcription. Our data showed that BPAF-induced transcription could be significantly blocked by PP2, PD98059 and U0126, suggesting activation of ERK1/2 was also required to regulate endogenous transcription. Taken together, these results indicate that BPAF-induced endogenous transcription of estrogen responsive genes is mediated through both genomic and nongenomic pathways involving the ER? and ERK1/2 activation in human breast cancer cells.

SUBMITTER: Li M 

PROVIDER: S-EPMC3984236 | BioStudies | 2014-01-01

REPOSITORIES: biostudies

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